ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.1178A>C (p.His393Pro) (rs118203944)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424623 SCV000517248 pathogenic not provided 2015-05-27 criteria provided, single submitter clinical testing The H393P variant in the ARSB gene is a common MPS VI variant that has been reported in thehomozygous and the compound heterozygous state in multiple unrelated individuals withmucopolysaccharidosis type VI (MPS VI). Patients with the H393P variant who were compoundheterozygous for different missense variants were reported with variable disease severity (Litjens et al.,1996; Karageorgos et al., 2007). Functional studies of the H393P substitution indicate that it is a severe nullallele resulting in an undetectable enzyme level (Litjens et al., 1996). The H393P variant was notobserved with any significant frequency in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variantin these populations. The H393P variant is a non-conservative amino acid substitution, which occurs at aposition that is conserved across species. Missense variants in nearby residues (E390K and F399L) havebeen reported in the Human Gene Mutation Database in association with MPS VI (Stenson et al., 2014),supporting the functional importance of this region of the protein. We interpret H393P as a pathogenic variant.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000000934 SCV000802966 uncertain significance Mucopolysaccharidosis type VI 2018-01-01 criteria provided, single submitter curation Very low frequency in ExAC (PM2); Reputable source identifies as pathogenic (PP5)
OMIM RCV000000934 SCV000021084 pathogenic Mucopolysaccharidosis type VI 1996-06-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.